The objective of the project is to study the mechanism of gelation of deoxyhemoglobin S and to find means of preventing deosyHb S polymerization. First, we continue testing the working hypothesis on the use of oligopeptides as potential antiaggregation agent, which differs from covalently bound compound that may cause side effects clinically. Second, the kinetics of the pregelation nucleation is perhaps more important than gelation per se. During the blood flow through microcirculation, a delay time of a few seconds in gelation for partially deoxygenated Hb S will prevent sickling inside the capillaries and therefore relieve the sickle cell crisis. Oligopeptides or other compounds will be tested for prolonging the lag period. Third, certain amino acids can reverse the shape of sickle cells to normal biconcave disks in vitro, although these compounds do not raise the minimum gelling concentration (MGC) of deoxyHb S. The relationship between deoxyHb S gelation and cell deformability is therefore relevant to this "puzzle." The work outlined under the first two objectives will be done by laser light scattering, which determines both the molecular weight and diffusion coefficient of the protein molecules. The technique used for the third objectivee will be electron microscopy, including autoradiography.